SUNLIGHT: Phase III Study of Trifluridine/Tipiracil in Combination With Bevacizumab vs Trifluridine/Tipiracil Single Agent in Patients With Refractory Metastatic Colorectal Cancer
Study Details
Study Description
Brief Summary
This study is designed as an international, open-label, controlled two-arm, randomized phase III comparison study evaluating the efficacy and safety of trifluridine/tipiracil in combination with bevacizumab versus trifluridine/tipiracil monotherapy in patients with refractory mCRC.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 3 |
Detailed Description
This is an international, open-label, controlled two-arm, randomised phase III study evaluating the efficacy and safety of trifluridine/tipiracil in combination with bevacizumab versus trifluridine/tipiracil monotherapy in patients with refractory mCRC. The analysis will be done after 331 events are reported. In order to observe this number of events, 490 patients will be randomised (1:1) to receive trifluridine/tipiracil in combination with bevacizumab (experimental arm) or trifluridine/tipiracil monotherapy (control arm).
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: trifluridine/tipiracil in combination with bevacizumab
|
Drug: Trifluridine/Tipiracil
Taken by mouth two times a day, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest
Other Names:
Drug: Bevacizumab
administered every 2 weeks (Day 1 and Day 15)
Other Names:
|
| Active Comparator: trifluridine/tipiracil monotherapy
|
Drug: Trifluridine/Tipiracil
Taken by mouth two times a day, 5 days on/2 days off, over 2 weeks, followed by a 14-day rest
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Overall Survival (OS) [Approximately 12 months]
Overall survival defined as the observed time elapsed between the date of randomization and the date of death due to any cause
Secondary Outcome Measures
- Progression-free survival (PFS) [Approximately 12 months]
Progression-free survival defined as the time elapsed between the randomization and the date of radiologic tumour progression according to RECIST version 1.1 (Eisenhauer, 2009) by investigator's judgement or death from any cause, whichever comes first.
- Overall response rate (ORR) [Approximately 12 months]
Overall response rate defined as the proportion of patients with objective evidence of complete response (CR) or partial response (PR) according to RECIST version 1.1 criteria and using investigator's tumor assessment
- Disease control rate (DCR) [Approximately 12 months]
Disease control rate defined as the proportion of patients with objective evidence of CR or PR or stable disease (SD) according to RECIST version 1.1 criteria and using investigator's tumor assessment
- Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0, including serious adverse events (SAEs) for safety and tolerability assessment of study drug(s) [Approximately 12 months]
Treatment-emergent adverse events (TEAEs) as assessed by CTCAE v5.0, including serious adverse events (SAEs)
- Quality of life: EORTC QLQ-C30 [Approximately 12 months]
Assess patients health and activities using the European Organization for Research and Treatment of Cancer Core Quality of Life (EORTC QLQ-C30) module.
- Quality of life: EQ-5D-5L [Approximately 12 months]
Assess patients health and activities using the European Organization for Research and Treatment of Cancer Core Quality of Life (EQ-5D-5L) module.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has histologically confirmed unresectable adenocarcinoma of the colon or rectum (all other histological types are excluded).
-
RAS status must have been previously determined (mutant or wild-type) based on local assessment of tumor biopsy.
-
Has received a maximum of 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer and had demonstrated progressive disease or intolerance to their last regimen.
-
Has measurable or non-measurable disease as defined by RECIST version 1.1
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Is able to swallow oral tablets.
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Estimated life expectancy ≥12 weeks.
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Eastern Cooperative Oncology Group performance status (ECOG PS) 0 or 1
Exclusion Criteria:
-
More than 2 prior chemotherapy regimens for the treatment of advanced colorectal cancer.
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Pregnancy, lactating female or possibility of becoming pregnant during the study.
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Patients currently receiving or having received anticancer therapies within 4 weeks prior to randomization.
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Has not recovered from clinically relevant non-hematologic CTCAE grade ≥ 3 toxicity of previous anticancer therapy prior to randomization (excluding alopecia, and skin pigmentation).
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Has symptomatic central nervous system metastases that are neurologically unstable or requiring increasing doses of steroids to control CNS disease.
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Has severe or uncontrolled active acute or chronic infection.
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Has active or history of interstitial lung disease and/or pneumonitis, or pulmonary hypertension.
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Known Hepatitis B or Hepatitis C Virus infection.
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Known carriers of HIV antibodies.
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Confirmed uncontrolled arterial hypertension (defined as systolic blood pressure ≥ 150 mm Hg and/or diastolic blood pressure ≥ 100 mm Hg) or uncontrolled or symptomatic arrhythmia.
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Deep arterial thromboembolic events including cerebrovascular accident or myocardial infarction within the last 6 months prior to randomization.
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Treatment with any of the following within the specified time frame prior to randomization:
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major surgery within 4 weeks prior to randomisation (the surgical incision should be fully healed prior to study drug administration), or has not recovered from side effects of previous surgery, or patient that may require major surgery during the study
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Prior radiotherapy if completed less than 4 weeks before randomisation, except if provided as a short course for symptoms palliation only.
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Drainage for ascites, pleural effusion or pericardial fluid within 4 weeks prior to randomization
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Other clinically significant medical conditions.
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Other malignancies.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Mayo Clinic - AZ | Phoenix | Arizona | United States | 85054 |
| 2 | CARTI Cancer Center | Little Rock | Arkansas | United States | 72205 |
| 3 | City of Hope | Duarte | California | United States | 91010 |
| 4 | City of Hope - South Pasedena | South Pasadena | California | United States | 91030 |
| 5 | City of Hope - Upland | Upland | California | United States | 91786 |
| 6 | Mayo Clinic - FL | Jacksonville | Florida | United States | 32224 |
| 7 | Mount Sinai Comprehensive Cancer Center | Miami Beach | Florida | United States | 33140 |
| 8 | Comprehensive Hematology Oncology | Saint Petersburg | Florida | United States | 33709 |
| 9 | DuPage Medical Group - Joliet Oncology-Hematology Associates | Joliet | Illinois | United States | 60435 |
| 10 | Investigative Clinical Research - Indianapolis | Noblesville | Indiana | United States | 46062 |
| 11 | Mayo Clinic - MN | Rochester | Minnesota | United States | 55905 |
| 12 | Oncology Hematology West, PC dba Nebraska Cancer Specialists | Omaha | Nebraska | United States | 68130 |
| 13 | "Medizinische Universität Graz " | Graz | Austria | 8036 | |
| 14 | "Medizinische Universität Innsbruck Univ.-Klinik für Innere Medizin V" | Innsbruck | Austria | 6020 | |
| 15 | "Ordensklinikum Linz Barmherzige Schwestern Interne I" | Linz | Austria | 4010 | |
| 16 | "Landeskrankenhaus Feldkirch Interne E" | Rankweil | Austria | 6830 | |
| 17 | "Landeskrankenhaus (SALK) Universitätsklinik für Innere Medizin III (SALK)" | Salzburg | Austria | 5020 | |
| 18 | "Landesklinikum Wiener Neustadt " | Wiener Neustadt | Austria | 2700 | |
| 19 | "Allgemeines Krankenhaus - Universitätskliniken Klinische Abteilung für Onkologie" | Wien | Austria | 1090 | |
| 20 | "OLV Ziekenhuis Oncology" | Aalst | Belgium | 9300 | |
| 21 | "Universitair Ziekenhuis Antwerpen Oncologie" | Edegem | Belgium | 2650 | |
| 22 | "UZ Leuven Campus Gasthuisberg Digestieve Oncologie" | Leuven | Belgium | 3000 | |
| 23 | "CHC Montlégia Oncologie" | Liege | Belgium | 4000 | |
| 24 | "AZ NIKOLAAS Oncology" | Sint Niklaas | Belgium | 9100 | |
| 25 | "Hospital do Câncer de Barretos - Fundação Pio XII Unidade de Pesquisa Clínica" | Barretos | Brazil | 14784-400 | |
| 26 | "Hospital de Base Centro Integrado de Pesquisa" | Sao Jose Do Rio Preto | Brazil | 15090-000 | |
| 27 | "ICESP - Instituto do Câncer do Estado de São Paulo Centro Integrado de Pesquisa" | Sao Paulo | Brazil | 01246-000 | |
| 28 | "Hospital A C Camargo Unidade de Pesquisa Clinica" | Sao Paulo | Brazil | 01509-900 | |
| 29 | "Instituto Brasileiro de Controle do Câncer Unidadde de Pesquisa Clínica" | Sao Paulo | Brazil | 03102-002 | |
| 30 | "Hospital Albert Einstein Instituto de Ensino e Pesquisa" | Sao Paulo | Brazil | 05652- 900 | |
| 31 | "Aalborg Universitetshospital, Syd Onkologisk Afdeling" | Aalborg | Denmark | 9000 | |
| 32 | Rigshospitalet Dpt of Oncology | Copenhagen | Denmark | 2100 | |
| 33 | "Regionshospitalet Herning, Hospitalsenheden Vest Onkologisk Afdeling" | Herning | Denmark | 7400 | |
| 34 | "Odense Universitetshospital Department of Oncology" | Odense | Denmark | 5000 | |
| 35 | "CHU Jean Minjoz Service d'oncologie médicale" | Besancon | France | 25030 | |
| 36 | "CHU Morvan Institut de Cancérologie et d'Hématologie" | Brest | France | 29200 | |
| 37 | "Centre de lutte contre le cancer Francois Baclesse UCP Digestif" | Caen | France | 14076 | |
| 38 | "Hôpital Saint-Antoine Service d'Oncologie Médicale" | Paris | France | 75012 | |
| 39 | "Hôpital Européen Georges Pompidou Oncologie Hépatogastroenterologie-oncologie digestive" | Paris | France | 75015 | |
| 40 | "CHU de Poitiers Pole Régional de Cancérologie" | Poitiers | France | 86021 | |
| 41 | "Onkologische Schwerpunktpraxis Kurfuerstendamm " | Berlin | Germany | 10707 | |
| 42 | "Charite Universitätsmedizin Medizinische Klinik m.S. Haemat., Onko., Tumorimmunologie" | Berlin | Germany | 13353 | |
| 43 | Lübecker Onkologische Schwerpunktpraxis im Hochschulstadttei | Luebeck | Germany | 23562 | |
| 44 | "Klinikum der Universität München Campus Großhadern, Medizinische Klinik und Poliklinik III" | Muenchen | Germany | 81377 | |
| 45 | "Magyar Honvedseg Egeszsegugyi Kozpont Onkologiai Osztaly" | Budapest | Hungary | 1062 | |
| 46 | "Szent Imre Egyetemi Oktatokorhaz Klinikai Onkologiai Osztaly" | Budapest | Hungary | 1115 | |
| 47 | "Orszagos Onkologiai Intezet "B" Belgyogyaszati-Onkologiai O. Es Klin. Farmakologiai O." | Budapest | Hungary | 1122 | |
| 48 | "Debreceni Egyetem Orvos es Egeszsegtudomanyi Centrum Onkologiai Intezet" | Debrecen | Hungary | 4032 | |
| 49 | "Bekes Megyei Kozponti Korhaz Onkologia" | Gyula | Hungary | 5700 | |
| 50 | Petz Aladar Megyei Oktato Korhaz Onkoradiologiai Osztaly | Győr | Hungary | 9024 | |
| 51 | Bacs-Kiskun Megyei Korhaz Onkoradiologiai Kozpont | Kecskemét | Hungary | 6000 | |
| 52 | "Szegedi Tudomanyegyetem Szent-Gyorgyi Albert Klinikai Kp. Onkoterápiás Klinika" | Szeged | Hungary | 6720 | |
| 53 | "JNSZ Megyei Hetenyi Geza Korhaz es Rendelointezet Megyei Onkologiai Centrum" | Szolnok | Hungary | 5004 | |
| 54 | "Markusovszky Egyetemi Oktatokorhaz Onkoradiologiai Osztaly" | Szombathely | Hungary | 9700 | |
| 55 | Oncologia Medica A.O. Universitaria di Cagliari Policlinico Universitario "Duilio Casula" di Monserrato" | Monserrato | Italy | 9042 | |
| 56 | S.C. di Oncologia Medica Addominale Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale" | Napoli | Italy | 80131 | |
| 57 | U.O.C. OncoEmatologia Dipartimento di Medicina di Precisione c/o Nuovo Policlinico Università degli studi della Campania "Luigi Vanvitelli" | Napoli | Italy | 80131 | |
| 58 | Unità Operativa Complessa Oncologia Medica 1 Istituto Oncologico Veneto - IRCCS" | Padova | Italy | 35128 | |
| 59 | "U.O. di Oncologia Medica Polo Oncologico Edificio 22 Stabilimento Santa Chiara AZ. Osped. Universitaria Pisana" | Pisa | Italy | 56126 | |
| 60 | U.O. Oncologia Medica Azienda Ospedaliera Regionale - Potenza Ospedale "San Carlo" - Potenza | Potenza | Italy | 85100 | |
| 61 | "S.C. Oncologia - Responsabile S.S. Sperimentazioni Cliniche ASMN - IRCCS di Reggio Emilia" | Reggio Emilia | Italy | 42123 | |
| 62 | Unità Operativa di Oncologia ed Ematologia Istituto Clinico Humanitas" | Rozzano (MI) | Italy | 20089 | |
| 63 | Dipartimento di Onco-Ematologia Ospedale IRCSS Casa Sollievo della Sofferenza" | San Giovanni Rotondo | Italy | 71013 | |
| 64 | Przychodnia Lekarska "KOMED" | Konin | Poland | 62-500 | |
| 65 | "SP ZOZ Szpital Uniwersytecki w Krakowie Oddzial Kliniczny Onkologii" | Krakow | Poland | 31-531 | |
| 66 | "Opolskie Centrum Onkologii im. Tadeusza Koszarowskiego Oddzial Onkologii Klinicznej" | Opole | Poland | 45-061 | |
| 67 | "Wojewodzki Szpital Specjalistyczny im. Janusza Korczaka w Slupsku Sp. z o.o." | Słupsk | Poland | 76-200 | |
| 68 | "Narodowy Instytut Onkologii im. Marii Skłodowskiej-Curie Państwowy Instytut Badawczy Klinika Onkologii i Radioterapii" | Warszawa | Poland | 02-034 | |
| 69 | "Wojskowy Instytut Medyczny Klinika Onkologii" | Warszawa | Poland | 04-141 | |
| 70 | "Centralny Szpital Kliniczny MSWiA Oddział Radioterapii i Onkologii" | Warzszawa | Poland | 02-507 | |
| 71 | Pan American Center for Oncology Trials, LLC | Río Piedras | Puerto Rico | 00935 | |
| 72 | "Arkhangelsk Clinical Oncology Dispensary chemotherapy department" | Arkhangelsk | Russian Federation | 163045 | |
| 73 | "Clinical Oncology Dispensary No.1 Chemotherapy Department" | Krasnodar | Russian Federation | 350040 | |
| 74 | "Kursk Regional Clinical Oncology Dispensary General Oncology Department" | Kursk | Russian Federation | 305524 | |
| 75 | "Moscow City Oncology Hospital # 62 chemotherapy department" | Moscow Region | Russian Federation | 143423 | |
| 76 | "Russian Cancer Research Center n.a. NN Blokhin Clinical Pharmacology and Chemotherapy" | Moscow | Russian Federation | 115478 | |
| 77 | "University Headache Clinic Outpatient oncology clinic" | Moscow | Russian Federation | 121467 | |
| 78 | "National Medical Research Centre of Radiology Moscow Research Oncology Institute N.A. Herzen" | Moscow | Russian Federation | 125284 | |
| 79 | "Omsk Clinical Oncologic Dispensary Chemotherapy" | Omsk | Russian Federation | 644046 | |
| 80 | "National Medical Research Center of Oncology N.N. Petrova " | Saint-petersburg | Russian Federation | 197758 | |
| 81 | "Multidisciplinary clinic "Reaviz" " | Samara | Russian Federation | 443011 | |
| 82 | "Oncology dispensary No.2 Oncology department" | Sochi | Russian Federation | 354057 | |
| 83 | "Scientific Centre for Specialized Medical Care (oncological) Chemotherapy" | St Petersburg | Russian Federation | 115478 | |
| 84 | "Saint Petersburg City Oncology Clilnic " | St Petersburg | Russian Federation | 198255 | |
| 85 | SBIH of YR ""Clinical oncology hospital chemotherapy department" | Yaroslavl | Russian Federation | 150054 | |
| 86 | "H. Valle de Hebrón Servicio de Oncología - (VHIR)" | Barcelona | Spain | 08035 | |
| 87 | "Hospital de la Santa Creu I Sant Pau Oncología Medica" | Barcelona | Spain | 08041 | |
| 88 | "Hospital Uni. Reina Sofía - Hospital Provincial Departamento de Oncología Médica" | Cordoba | Spain | 14004 | |
| 89 | "INSTITUTO CATALAN DE ONCOLOGÍA - ICO Oncología Médica" | Hospitalet de Llobregat | Spain | 08908 | |
| 90 | "Hospital Universitario Ramón y Cajal Servicio de Oncologia Médica" | Madrid | Spain | 28034 | |
| 91 | "HOSPITAL 12 DE OCTUBRE Servicio Oncología Médica" | Madrid | Spain | 28041 | |
| 92 | "Hospital Universitario Marqués de Valdecilla oncología medica" | Santander | Spain | 39008 | |
| 93 | "H.VIRGEN DEL ROCIO Servicio de Oncología Médica" | Sevilla | Spain | 41013 | |
| 94 | "H. GENERAL DE VALENCIA Servicio de Oncología Médica" | Valencia | Spain | 46014 | |
| 95 | "Hospital Universitario Miguel Servet Edif. de maternidad planta 8. Servicio de Oncología Médica " | Zaragoza | Spain | 50009 | |
| 96 | Kyiv City Clinical Oncological Centre | Kiev | Ukrain | Ukraine | 03115 |
| 97 | "Cherkasy Regional Oncological Dispensary Regional Clinical Oncological Centre" | Cherkassy | Ukraine | 18009 | |
| 98 | "MI ""Dnipropetrovsk City Multi-field Clinical Hospital #4"" Department of Oncology" | Dnipro | Ukraine | 49102 | |
| 99 | "LLC Ukrainian Center of Tomotherapy "Tomoclinic", Chemoteraphy Department" | Kropyvnytskyi | Ukraine | 25011 | |
| 100 | "National Cancer Institute Department of minimally invasive and endoscopic surgery, interventional radiology " | Kyiv | Ukraine | 03022 | |
| 101 | "Medical Center n.a. Acad. Spizhenko "Syber Clinic Spizhenko"" Department of Oncology" | Kyiv | Ukraine | 08112 | |
| 102 | "Clinical and diagnostic Centre of Medics-rey Inter. Group LLC Hospital of Israeli Oncology "LISOD" | Kyiv | Ukraine | 08720 | |
| 103 | "Podillia Regional Oncology Centre Chemotherapy Department" | Vinnitsya | Ukraine | 21029 |
Sponsors and Collaborators
- Taiho Oncology, Inc.
- Institut de Recherches Internationales Servier
Investigators
- Principal Investigator: Josep Tabernero, Prof, Vall d'Hebron Institute of Oncology
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- CL3-95005-007
- 2020-001976-14